Targeting for stereotactic radiosurgical thalamotomy based on tremor treatment response

OBJECTIVE Stereotactic radiosurgery (SRS) treats severe, medically refractory essential tremor and tremor-dominant Parkinson disease. However, the optimal target for SRS treatment within the thalamic ventral intermediate nucleus (VIM) is not clearly defined. This work evaluates the precision of the physician-selected VIM target, and determines the optimal SRS target within the VIM by correlation between early responders and nonresponders. METHODS Early responders and nonresponders were assessed retrospectively by Elements Basal Ganglia Atlas autocontouring of the VIM on the pre–SRS-treatment 1-mm slice thickness T1-weighted MRI and correlating the center of the post–SRS-treatment lesion. Using pre- and posttreatment diffusion tensor imaging, the fiber tracking package in the Elements software generated tremor-related tracts from autosegmented motor cortex, thalamus, red nucleus, and dentate nucleus. Autocontouring of the VIM was successful for all patients. RESULTS Among 23 patients, physician-directed SRS targets had a medial–lateral target range from +2.5 mm to −2.0 mm from the VIM center. Relative to the VIM center, the SRS isocenter target was 0.7–0.9 mm lateral for 6 early responders and 0.9–1.1 mm medial for 4 nonresponders (p = 0.019), and without differences in the other dimensions: 0.2 mm posterior and 0.6 mm superior. Dose–volume histogram analyses for the VIM had no significant differences between responders and nonresponders between 20 Gy and 140 Gy, mean or maximum dose, and dose to small volumes. Tractography data was obtained for 4 patients. CONCLUSIONS For tremor control in early responders, the Elements Basal Ganglia Atlas autocontour for the VIM provides the optimal SRS target location that is 0.7–0.9 mm lateral to the VIM center.

Track-Density Ratio Mapping With Fiber Types in the Cerebral Cortex Using Diffusion-Weighted MRI

The nerve fibers are divided into three categories: projection, commissural, and association fibers. This study demonstrated a novel cortical mapping method based on these three fiber categories using MR tractography data. The MR fiber-track data were extracted using the diffusion-weighted 3T-MRI data from 19 individuals’ Human Connectome Project dataset. Anatomical MR images in each dataset were parcellated using FreeSurfer software and Brainnetome atlas. The 5 million extracted tracks per subject by MRtrix software were classified based on the basic cortical structure (cortical area in the left and right hemisphere, subcortical area), after the tracks validation procedure. The number of terminals for each categorized track per unit-sized cortical area (1 mm3) was defined as the track-density in that cortical area. Track-density ratio mapping with fiber types was achieved by mapping the density-dependent color intensity for each categorized tracks with a different primary color. The mapping results showed a highly localized, unique density ratio map determined by fiber types. Furthermore, the quantitative group data analysis based on the parcellation information revealed that the majority of nerve fibers in the brain are association fibers, particularly in temporal, inferior parietal, and occipital lobes, while the projection and commissural fibers were mainly located in the superior part of the brain. Hemispheric asymmetries in the fiber density were also observed, such as long association fiber in the Broca’s and Wernicke’s areas. We believe this new dimensional brain mapping information allows us to further understand brain anatomy, function.

Multicenter Prospective Analysis of Hypertrophic Olivary Degeneration Following Infratentorial Stroke (HOD-IS): Evaluation of Disease Epidemiology, Clinical Presentation, and MR-Imaging Aspects

Introduction: Ischemic and hemorrhagic strokes in the brainstem and cerebellum with injury to the functional loop of the Guillain-Mollaret triangle (GMT) can trigger a series of events that result in secondary trans-synaptic neurodegeneration of the inferior olivary nucleus. In an unknown percentage of patients, this leads to a condition called hypertrophic olivary degeneration (HOD). Characteristic clinical symptoms of HOD progress slowly over months and consist of a rhythmic palatal tremor, vertical pendular nystagmus, and Holmes tremor of the upper limbs. Diffusion Tensor Imaging (DTI) with tractography is a promising method to identify functional pathway lesions along the cerebello-thalamo-cortical connectivity and to generate a deeper understanding of the HOD pathophysiology. The incidence of HOD development following stroke and the timeline of clinical symptoms have not yet been determined in prospective studies—a prerequisite for the surveillance of patients at risk.Methods and Analysis: Patients with ischemic and hemorrhagic strokes in the brainstem and cerebellum with a topo-anatomical relation to the GMT are recruited within certified stroke units of the Interdisciplinary Neurovascular Network of the Rhine-Main. Matching lesions are identified using a predefined MRI template. Eligible patients are prospectively followed up and present at 4 and 8 months after the index event. During study visits, a clinical neurological examination and brain MRI, including high-resolution T2-, proton-density-weighted imaging, and DTI tractography, are performed. Fiberoptic endoscopic evaluation of swallowing is optional if palatal tremor is encountered.Study Outcomes: The primary endpoint of this prospective clinical multicenter study is to determine the frequency of radiological HOD development in patients with a posterior fossa stroke affecting the GMT at 8 months after the index event. Secondary endpoints are identification of (1) the timeline and relevance of clinical symptoms, (2) lesion localizations more prone to HOD occurrence, and (3) the best MR-imaging regimen for HOD identification. Additionally, (4) DTI tractography data are used to analyze individual pathway lesions. The aim is to contribute to the epidemiological and pathophysiological understanding of HOD and hereby facilitate future research on therapeutic and prophylactic measures.Clinical Trial Registration: HOD-IS is a registered trial at https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020549.

Pathology of microstructural brain connectivity in paranoid schizophrenia (according to diffusion-tensor tractography data)

AIM: revealing microstructural brain connectivity alterations in patients with paranoid schizophrenia. MATERIALS AND METHODS: 25 patients diagnosed with paranoid schizophrenia were examined. The control group was 30 healthy people without neurological and somatic diseases. Studies were carried out on the Philips Ingenia magnetic resonance tomograph, with a magnetic field strength of 1.5 T using the DTI pulse sequence. Data processing was carried out using the tractographic module DSI Studio. RESULTS: According to the group assessment of the obtained tractographic brain data, significant differences in microstructural connectivity in the group of patients with paranoid schizophrenia were detected. A pathological conglomerate of cortical-subcortical structure connectivity was found, different from the sets of normal connections in the control group, consisting of a cingulate gyrus, hippocampus and thalamus. Such a pathological control center is one of the possible tractographic patterns of schizophrenia. In our opinion, the pathological connectivity of the hippocampus and thalamus, as one of the main components of the limbic system of the brain, reduces the controlling emotional function of the cingulate cortex, the control center of this system. In this case, excessive connectivity of the hippocampus with the cingulate cortex may indicate an incorrect implementation of their interaction, which also affects the occurrence or progression of emotional-will disorders. The thalamus, being the center of transmission of sensory and motor information from the sensory organs, can transmit incorrect redundant data about what is happening around the body and participate in the formation of auditory and visual hallucinations. Also, the pathological work of the thalamus may be involved in the progression of autism. Thus, the patient is increasingly losing touch with reality, increasingly preferring unknowingly fantasy, erasing ties with reality. Data from one of the characteristics of the artiformal neural network the clustering coefficient were significantly increased in patients compared to the control group, which may indicate the presence of excess, abnormal microstructural connectivity in the network. CONCLUSION: The study confirms the presence of microstructural and neural network changes in the hippocampus, thalamus, cingulate cortex and basal ganglia. These changes are peculiar tractographic semiotic signs of brain pathology in paranoid schizophrenia. This study is a step in the search for a tool to identify the features of neuroplasticity disorders in this disease and schizophrenia screening (2 figures, 3 tables, bibliography: 13 refs).

The quantitative evaluation of cortico-spinal tract involvement in malignant intracerebral tumors

The aim of the study was development of the method for preoperative quantitative evaluation of pyramidal tract and tumor relationship in malignant intracerebral tumors.Materials and methods. The retrospective analysis of 62 patients underwent surgery at the Department of Neurosurgery of Privolzhsky Research Medical University in 2017–2019, was performed. The patients were divide in 3 groups: metastatic brain tumor (n = 16); contrast-enhanced gliomas (grade III–IV); contrast-nonenhanced gliomas (grade II–III). The following protocol was implemented for all patients: preoperative DTI-tractography; intraoperative direct subcortical electrical stimulation with fixation of the minimum current intensity at receiving the motor response; pre- and postoperative motor function assessment using MRC-scale. Tract Involvement Index (TII) based on the ratio of the perimeter of the part of the tract involvement in pathological MRI-signal to its cross-section area was calculated using image processing of preoperative MRI and MRI-tractography data.Results. The association between TII values (from 0 to 1.75) and the severity of pre-operative paresis was demonstrated. We have discovered that the greater value of the pyramidal TII was corresponded to the greater severity of the paresis in MRC (p <0.001, n = 62). The analysis of TII values and intraoperative motor direct subcortical mapping results showed an increase in risk of contact with a tract at higher TII value (B0 = −1.6; Bi = 6.61; χ2 = 30.53; n = 62, p <0.001). The TII demonstrates better prognostic value in patients without radiation therapy in anamnesis.Conclusions. The method for preoperative quantitative evaluation of pyramidal tract and tumor relationship using TII calculation can provide additional information for planning surgical treatment in patients with intracerebral tumors without radiation treatment in the history.

Shift Toward Randomness in Brain Networks of Patients With Anorexia Nervosa: The Role of Malnutrition

No study to date investigated structural white matter (WM) connectome characteristics in patients with anorexia nervosa (AN). Previous research in AN found evidence of imbalances in global and regional connectomic brain architecture and highlighted a role of malnutrition in determining structural brain changes. The aim of our study was to explore the characteristics of the WM network architecture in a sample of patients with AN. Thirty-six patients with AN and 36 healthy women underwent magnetic resonance imaging to obtain a high-resolution three-dimensional T1-weighted anatomical image and a diffusion tensor imaging scan. Probabilistic tractography data were extracted and analyzed in their network properties through graph theory tools. In comparison to healthy women, patients with AN showed lower global network segregation (normalized clustering: p = 0.029), an imbalance between global network integration and segregation (i.e., lower small-worldness: p = 0.031), and the loss of some of the most integrative and influential hubs. Both clustering and small-worldness correlated with the lowest lifetime body mass index. A significant relationship was found between the average regional loss of cortical volume and changes in network properties of brain nodes: the more the difference in the cortical volume of brain areas, the more the increase in the centrality of corresponding nodes in the whole brain, and the decrease in clustering and efficiency of the nodes of parietal cortex. Our findings showed an unbalanced connectome wiring in AN patients, which seems to be influenced by malnutrition and loss of cortical volume. The role of this rearrangement in the maintenance and prognosis of AN and its reversibility with clinical improvement needs to be established by future studies.

Brain Small-Worldness Properties and Perceived Fatigue in Mild Cognitive Impairment

Background Perceived fatigue is among the most common complaints in older adults and is substantially influenced by diminished resources or impaired structure of widespread cortical and subcortical regions. Alzheimer’s disease and its preclinical stage – mild cognitive impairment (MCI) – is considered a brain network disease. It is unknown, however, whether those with MCI will therefore perceive worse fatigue, and whether an impaired global brain network will worsen their experience of fatigue. Methods In this pilot case-control study of age-, sex-, and education-matched MCI and their cognitively healthy counterparts (HC), perceived fatigue was measured using Multidimensional Fatigue Inventory, and diffusion tensor imaging (DTI) tractography data was analyzed using graph theory methods to explore small-worldness properties: segregation and integration. Results Perceived fatigue was more severe in MCI than HC. Despite a trend for greater network alterations in MCI, there were no significant group differences in integration or segregation. Greater perceived fatigue was related to higher segregation across groups; more perceived fatigue was related to higher segregation and lower integration in MCI but not HC. Conclusions Findings of the present study support the notion that altered whole-brain small-worldness properties in brain aging or neurodegeneration may underpin perceived fatigue.

Structural brain network topology underpinning ADHD and response to methylphenidate treatment

Behavioural disturbances in attention deficit hyperactivity disorder (ADHD) are thought to be due to dysfunction of spatially distributed, interconnected neural systems. While there is a fast-growing literature on functional dysconnectivity in ADHD, far less is known about the structural architecture underpinning these disturbances and how it may contribute to ADHD symptomology and treatment prognosis. We applied graph theoretical analyses on diffusion MRI tractography data to produce quantitative measures of global network organisation and local efficiency of network nodes. Support vector machines (SVMs) were used for comparison of multivariate graph measures of 37 children and adolescents with ADHD relative to 26 age and gender matched typically developing children (TDC). We also explored associations between graph measures and functionally-relevant outcomes such as symptom severity and prediction of methylphenidate (MPH) treatment response. We found that multivariate patterns of reduced local efficiency, predominantly in subcortical regions (SC), were able to distinguish between ADHD and TDC groups with 76% accuracy. For treatment prognosis, higher global efficiency, higher local efficiency of the right supramarginal gyrus and multivariate patterns of increased local efficiency across multiple networks at baseline also predicted greater symptom reduction after 6 weeks of MPH treatment. Our findings demonstrate that graph measures of structural topology provide valuable diagnostic and prognostic markers of ADHD, which may aid in mechanistic understanding of this complex disorder.